The Role of Specific Retinoid Receptors in Sebocyte Growth and Differentiation in Culture1  Mi-Jung Kim, Nancy Ciletti, Robert L. Rosenfield  Journal of Investigative Dermatology  Volume 114, Issue 2, Pages 349-353 (February 2000) DOI: 10.1046/j.1523-1747.2000.00868.x Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Effect of ATRA and selective retinoid receptor agonists on sebocyte growth and differentiation in a primary rat preputial cell culture system. ATRA (all-trans retinoic acid), CD271 (adapalene, an RAR-β,γ agonist), CD2043 (RAR-α,β,γ pan-agonist), CD2809 (RXR agonist), and CD336 (RAR-α agonist). Means ± SEM are shown. ORO, Oil Red O. Effects on cell numbers (a), colony numbers (b), and differentiation (c). ATRA, CD271 (adapalene), and CD2043 decreased numbers of cells and colonies as well as LFCs, although the differences between these retinoids at 10−6 M were noteworthy: with ATRA, cell growth was inhibited but colonies became twice as differentiated as controls, whereas the RAR-β,γ agonist adapalene completely obliterated both cell growth and differentiation and the RAR pan-agonist CD2043 showed no more inhibitory effect than at 10−8 M. In contrast, the RXR agonist CD2809 increased numbers of cells and LFCs, with no effect on colony numbers. Treatment with the RAR-α agonist CD336, performed in a different set of experiments, significantly decreased both cell numbers and LFCs. Journal of Investigative Dermatology 2000 114, 349-353DOI: (10.1046/j.1523-1747.2000.00868.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Effect of ATRA and selective retinoid receptor agonists on preputial cell morphology in monolayer culture. Scanning power (a;scale bar: 400 μm) and high power (b;scale bar: 50 μm) views of sebocyte colonies on day 9 are shown. Oil Red O stain. Compared with controls, the reduced number of colonies remaining after high dose ATRA (10−6 M) were distorted and contained numerous misshapen cells, many of which seemed mid-differentiated or degenerating. Colonies treated with 10−7 M RAR-β,γ agonist (CD271, adapalene) were smaller than controls, and many cells were undifferentiated and had become distorted and fibroblast-like in shape. In contrast, colonies treated with 10−6 M RXR agonist (CD2809) were bigger and contained numerous mid-differentiated sebocytes. Journal of Investigative Dermatology 2000 114, 349-353DOI: (10.1046/j.1523-1747.2000.00868.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Effect of the RAR-β,γ antagonist on proliferation and differentiation of preputial sebocytes treated with ATRA or selective RAR agonists. (a) Proliferation; (b) differentiation. Means ± SEM are shown. The RAR-β,γ antagonist CD2665 abrogated both the antiproliferative and antidifferentiative effects of ATRA, CD271 (adapalene, an RAR-β,γ agonist), and CD2043 (RAR-α,β,γ pan-agonist), returning cell numbers and percent LFCs to control levels. CD2665 alone had no significant effects on cell proliferation and differentiation at 10−7 M. Journal of Investigative Dermatology 2000 114, 349-353DOI: (10.1046/j.1523-1747.2000.00868.x) Copyright © 2002 The Society for Investigative Dermatology, Inc Terms and Conditions